CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials

Our plain-English summary of CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials, by N.K. Chintala, D. Restle, H. Quach, et al (Lung Cancer, 2021).

The study

• Authors: N.K. Chintala, D. Restle, H. Quach, J. Saini, R. Bellis, M. Offin, J. Beattie, P.S. Adusumilli
• Journal: Lung Cancer
• Published: 2021;157:48-59
• Type of article: Review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The aim of adoptive T-cell therapy is to promote tumor-infiltrating immune cells following the transfer of either tumor-harvested or genetically engineered T lymphocytes. A new chapter in adoptive T-cell therapy began with the success of chimeric antigen receptor (CAR) T-cell therapy. T cells harvested from peripheral blood are transduced with genetically engineered CARs that render the ability to recognize cancer cell-surface antigen and lyse cancer cells. The successes in CAR T-cell therapy for B-cell leukemia and lymphoma have led to efforts to expand this therapy to solid tumors. Herein, we discuss the rationale behind the preclinical development and clinical trials of T-cell therapies in patients with malignant pleural mesothelioma. Furthermore, we highlight the ongoing investigation of combination immunotherapy strategies to synergistically potentiate endogenous as well as adoptively transferred immunity.

Copyright © 2021 Elsevier B.V. All rights reserved.

In plain English

This article is a review by authors at Memorial Sloan Kettering Cancer Center of chimeric antigen receptor (CAR) T-cell therapy for malignant pleural mesothelioma. In this treatment, a patient's own T cells are genetically engineered to recognize a target on the surface of cancer cells, such as mesothelin, and kill them. The authors described laboratory work, including their own mouse experiments in which CAR T cells delivered into the pleural space worked better than intravenous delivery. They also summarized clinical trials. In one University of Pennsylvania trial, the best response was stable disease in 11 of 15 patients. A trial in 3 patients given FAP-targeted CAR T cells into the pleura reported no treatment-related toxicity. In the authors' own trial of 21 patients with pleural disease (19 with mesothelioma), the investigators reported a complete metabolic response on PET scanning in 2 patients, and no CAR T cell-related side effects above grade 2. The authors concluded that future research should combine CAR T cells with other immunotherapies. The review does not address asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of preclinical development and clinical trials of CAR T-cell therapy for malignant pleural mesothelioma
• Who was studied: Published preclinical studies and clinical trials of adoptive T-cell and CAR T-cell therapies, focused on patients with malignant pleural mesothelioma (MPM)
• Main results:
  • In the authors' mouse model of MPM, CAR T cells delivered into the pleural space were more effective than intravenous delivery
  • In an earlier University of Pennsylvania trial of mRNA-engineered mesothelin-targeted T cells, there was a transient partial response in 1 patient with mesothelioma and stable disease in 1 patient with pancreatic cancer
  • In a later University of Pennsylvania trial of mesothelin-targeted CAR T cells in patients with MPM, pancreatic cancer and ovarian cancer, the best response was stable disease in 11 of 15 patients, with no on-target/off-tumor toxicity
  • In a phase I trial, 3 patients received FAP-targeted CAR T cells by intrapleural injection; the treatment was reported as safe, without treatment-related toxicity
  • A National Cancer Institute trial of mesothelin-targeted CAR T cells, which included MPM, was stopped
  • The authors' own Memorial Sloan Kettering trial of intrapleural mesothelin-targeted CAR T cells enrolled 21 patients: 19 with MPM, 1 with lung cancer and 1 with breast cancer
  • In the Memorial Sloan Kettering trial, as interpreted by the investigator, 2 patients had a complete metabolic response on PET scanning, and no CAR T cell-related toxicities above grade 2 were observed
• The authors' conclusion: The authors concluded that future research on CAR T-cell therapy for MPM and other solid tumors should include combination immunotherapies that boost both the body's own immunity and the transferred immune cells

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Clinical Trial, Immunotherapy.

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